Forschungsdatenbank PMU-SQQUID

Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood-Brain Barrier.
Bauer, M; Römermann, K; Karch, R; Wulkersdorfer, B; Stanek, J; Philippe, C; Maier-Salamon, A; Haslacher, H; Jungbauer, C; Wadsak, W; Jäger, W; Löscher, W; Hacker, M; Zeitlinger, M; Langer, O;
Clin Pharmacol Ther. 2016; 100(2):13-41
Originalarbeiten (Zeitschrift)

Abstract/Keywords Web of Science PubMed PUBMED Central Full Text

PMU-Autor/inn/en

Jungbauer Christof

Abstract

A. Subjects underwent PET scans under conditions when ABCB1 and ABCG2 were functional and during ABCB1 inhibition with high-dose tariquidar. In contrast to the ABCB1-selective substrate (R)-[(11) C]verapamil, [(11) C]elacridar and [(11) C]tariquidar showed only moderate increases in brain distribution during ABCB1 inhibition. This provides evidence for a functional interplay between ABCB1 and ABCG2 at the human BBB and suggests that both ABCB1 and ABCG2 need to be inhibited to achieve substantial increases in brain distribution of dual ABCB1/ABCG2 substrates. During ABCB1 inhibition c.421CA subjects had significantly higher increases in [(11) C]tariquidar brain distribution than c.421CC subjects, pointing to impaired cerebral ABCG2 function.

Useful keywords (using NLM MeSH Indexing)

ATP Binding Cassette Transporter, Subfamily B/genetics

ATP Binding Cassette Transporter, Subfamily B/metabolism

ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics

ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism*

Acridines/pharmacokinetics

Adult

Blood-Brain Barrier/metabolism*

Brain/metabolism*

Female

Humans

Male

Neoplasm Proteins/genetics

Neoplasm Proteins/metabolism*

Pilot Projects

Polymorphism, Single Nucleotide

Positron-Emission Tomography/methods*

Quinolines/pharmacokinetics

Tetrahydroisoquinolines/pharmacokinetics

Tissue Distribution

Verapamil/metabolism

Verapamil/pharmacokinetics

Young Adult